The objective of the proposed research is to investigate the clonal nature and genetic origin of strains of Escherichia coli serotype 0157:H7, a newly described pathogen that has been epidemiologically linked to outbreaks and sporadic cases of hemorrhagic colitis in the United States and Canada. The mechanism by which this serotype causes bloody diarrhea/hemorrhagic colities is unknown, although the capacity to produce a cytotoxin similar to that of Shigella dysenteriae may be an important aspect of pathogenesis. The objective of this study is to determine the multilocus genotypes of 0157:H7 strains, through the detection of polymorphic proteins using multilocus enzyme electrophoresis and to test the hypothesis that recent outbreaks of hemorrhagic colitis are caused by organisms representing a single geographically-widespread clone. A second related aim is to determine the genetic relationships and evolutionary connections of 0157:H4 strains to other enteropathogenic serogroups and pathogenic forms of E. coli that are known to elaborate shiga-like cytotoxins. The results of the project will provide a population genetic framework for understanding the epidemiology and evolution of virulence factors in pathogenic E. coli help clarify the role of the organism in human disease. In addition, this investigation will serve as a foundation for study, on a global scale, of the genetic structure and evolutionary relationships of pathogenic E. coli that cause enteric disease in man and animals.